rs4813338

Positions:

• chr20-18664389-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080820.6(DTD1):​c.477+36156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,066 control chromosomes in the GnomAD database, including 16,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16672 hom., cov: 32)
• Consequence: DTD1 NM_080820.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTD1	NM_080820.6	c.477+36156A>G		intron_variant		ENST00000377452.4	NP_543010.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTD1	ENST00000377452.4	c.477+36156A>G		intron_variant		1	NM_080820.6	ENSP00000366672	P1
DTD1	ENST00000647441.1	c.*140+36156A>G		intron_variant, NMD_transcript_variant				ENSP00000493969

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69235 AN: 151948 Hom.: 16681 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 69244 AN: 152066 Hom.: 16672 Cov.: 32 AF XY: 0.461 AC XY: 34247 AN XY: 74330

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.437

Alfa AF: 0.504 Hom.: 32907

Bravo AF: 0.443

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4813338; hg19: chr20-18645033;